Differential effects of acute hypertriglyceridemia on insulin
action and insulin receptor autophosphorylation.
Gumbiner, Barry, Jeffrey F. Mucha, Jennifer E. Lindstrom, Ishali
Rekhi, James N. Livingston.
Department of Medicine, University of Rochester School of Medicine
and Dentistry, and Monroe Community Hospital, Rochester, NY, and
Institute for Metabolic Diseases, Miles Research Center, West Haven
CT
APStracts 2:0212E, 1995.
Experimentally-induced hypertriglyceridemia (HTG) and high plasma free
fatty acid (FFA) levels impair in vivo insulin action. To determine
if this is a consequence of impaired in vivo insulin receptor
autophosphorylation and related to defective receptor signaling,
hyperinsulinemic euglycemic clamps, indirect calorimetry and skeletal
muscle biopsies were performed in 9 healthy subjects. In vivo insulin
action was determined from the glucose infusion rate (GINF) and
glucose oxidation (Gox) during 40 and 120 mU/m2/min clamps with (HTG
clamp) and without (control clamp) a triglyceride emulsion infusion.
The percentage of receptors autophosphorylated in vivo was determined
by 125I-insulin tracer binding in skeletal muscle immunoprecipitates
of insulin receptors and phosphorylated receptors. Compared to the
control clamps, plasma triglycerides and FFAs increased 4- and 2-fold
while GINF and Gox decreased 15% and 35%, respectively, during the
HTG clamps (all p<0.05). However, the percentages of receptors
phosphorylated after the 40 and 120 mU/m2/min HTG clamps (9.2+1.5%
and 21.1+2.6%, respectively) were similar to the control clamps
(9.0+0.6% and 18.6+2.2%). These results indicate that if impaired
insulin signal transduction is a mechanism by which HTG and FFAs
impair insulin action, it occurs a site downstream from insulin
receptor autophosphorylation.
Received 6 August 1995; accepted in final form 4 October 1995
APS Manuscript Number E394-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95